Vol 50 No 4 Desember 2017.indd


188

Research Report

Dental Journal
(Majalah Kedokteran Gigi)
2017 December; 50(4): 188–193

The role of active ingredients nanopowder Stichopus hermanii 
gel to bone resorption in tension area of orthodontic tooth 
movement

Noengki Prameswari and Arya Brahmanta 
Departemen of Orthodontics
Faculty of Dentistry, Universitas Hang Tuah 
Surabaya - Indonesia

ABSTRACT

Background: Orthodontic tooth movement is a continual and balanced process between bone deposition and bone resorption 
in pressure and tension sites. Stichopus hermanii is one of the best fishery commodities in Indonesia. It is natural and contains 
various active ingredients such as hyaluronic acid, chondroitin sulphate, cell growth factor, eicosa pentaenoic acid (EPA) docosa 
hexaenoic acid (DHA) and flavonoid that potentially play a role in orthodontic tooth movement. Purpose: The aim of this study was 
to investigate the active ingredients of nanopowder Stichopus hermanii promoting bone resorption in tension area orthodontic tooth 
movement. Methods: A quantitative test for active ingredients of stichopus hermanii was conducted. Thirty two male Cavia cobaya 
were divisibled became four groups. K (–) groups as a negative control group (without treatment), K (+) groups as a positive control 
group which were provided with a separator rubber for orthodontic tooth movement, and P1, P2 groups, which were treated with 3% 
and 3.5% stichopus hermanii for orthodontic tooth movement. After treatment the cavia cobaya were sacrificed. TRAP-6 expression 
as a osteoclast marker was examined by means of an immunohistochemistry method. Results: A one-way Anova test confirmed that 
TRAP-6 expression was significantly increased with p = 0.00 (p≤0,05) in P2 compared to K (+). P2 to K (–), P2 to P1 and P1 to K 
(+) had no significant differences Conclusion: Nanopowder Stichopus hermanii 3.5% has an active ingredient that could increase 
osteoclast activity to resorb periodontal ligament and alveolar bone in tension areas of orthodontic tooth movement.

Keywords: Nanopowder; Stichopus hermanii; resorption; TRAP-6; orthodontic tooth movement 

Correspondence: Noengki Prameswari, Department of Orthodontic, Faculty of Dentistry, Universitas Hang Tuah. Jl. Arif Rahman 
Hakim 150 Surabaya, Indonesia. E-mail: noengki.prameswari@hangtuah.ac.id

INTRODUCTION

According to Riskesdas data of 2013, malocclusion 
is the third most common oral disease.1 Orthodontic 
treatment is generally associated with malocclusion that 
causes esthetic problems.2 Orthodontic tooth movement 
involving the use of orthodontic appliances is characterized 
by remodeling changes of the alveolar bone and a reaction 
of the periodontal ligament (PDL) to mechanical stimuli. 
Tooth movement occurs in the direction of force when there 
is a multifaceted bone remodelling response, with bone 
resorption on the compression side and bone apposition on 
the tension side of the periodontal ligament.3 

Orthodontic treatment for malocclusion correction 
requires a period of 1–2 years. Mechanically induced 
periodontal ligament and bone remodelling is still not 
fully understood. The role of the periodontal ligament 
has been questioned since tooth movement occurs. As 
long as an orthodontic appliance is applied, orthodontic 
movement occurs which can effect sequential reactions 
as respons of periodontal tissue and alveolar bone in 
remodeling and releasing of numerous mediators and 
substances from the periodontal and alveolar tissues and 
surrounding structures.4,5 After orthodontic mechanical 
pressure with both physical and biological characteristics, 
orthodontic tooth movement can occur either slowly or 
rapidly depending on its biological response.3

Dental Journal (Majalah Kedokteran Gigi) p-ISSN: 1978-3728; e-ISSN: 2442-9740. Accredited No. 32a/E/KPT/2017.
Open access under CC-BY-SA license. Available at http://e-journal.unair.ac.id/index.php/MKG
DOI: 10.20473/j.djmkg.v50.i4.p188–193

mailto:noengki.prameswari@hangtuah.ac.id
http://dx.doi.org/10.20473/j.djmkg.v50.i4.p188-193


189189Prameswari and Brahmanta/Dent. J. (Majalah Kedokteran Gigi) 2017 December; 50(4): 188–193

An orthodontic appliance can be defined as a mechanical 
stimulus resulting in biological celular response. Under 
orthodontic mechanical force, periodontal ligament 
responds with subsequent bone resorption in the area 
of pressure application and, conversely, under tension 
force will result in bone formation. An early response 
in the pressure area is one of periodontal ligament 
inflammation. When inflammation occurs, many cells are 
produced, including: cytokine, T-cell, B-cell, and matrix 
metalloproteinases (MMPs).6 Tissue reactions is also 
initiated immediately after force application in pressure 
and tension periodontal ligament. The extravasation and 
chemoattraction of numerous inflammatory cells begins, 
and followed by complex process of recruitment of 
osteoclast and osteoblast progenitors.3

Orthodontic appliances with varying degrees of 
frequency, magnitude, and duration of mechanical loading, 
result in extensive macroscopic and microscopic changes to 
the bone adjacent to periodontal tissues. Mechanical loading 
also alters periodontal tissue vascularity, metabolic process 
and blood flow resulting in the local synthesis and release 
of various molecules such as arachidonic acid, cytokines, 
growth factor, and colony-stimulating factors until tooth 
movement occurs.7 The released molecules as cellular 
responses in the various cell types in and around teeth, 
such as fibroblasts, osteoblasts, cementoblasts, and vascular 
cells as a stressor response of mechanical forces, provide 
a favourable microenvironment for tissue apposition or 
resorption in orthodontic tooth movement.3

When orthodontic forces are applied to the tooth, the 
resulting pressure will induce fibroblast cells, osteoclasts 
and osteoblas in periodontal ligament as a response to 
mechanical pressure. Orthodontic tooth movement is 
mediated by coupling mechanism between resorption 
and apposition process in the pressure and tension area 
of periodontal ligament and alveolar bone.3 Periodontal 
ligaments increase widening and induce bone remodeling 
so that orthodontic tooth movement occurs.8 Extracellular 
changes and crevicular gingival fluid as a biomarker 
orthodontic response occured.7 Collagen became the most 
important tissue in periodontal ligament remodeling. 
The ligament itself undergoes remodeling and the role of 
MMPs with their natural inhibitors, tissue inhibitors of 
metalloproteinases (TIMPs), are clearly of importance.6 
During orthodontic tooth movement, periodontal ligament 
remodeling followed with bone remodeling. Several 
enzymes such as alkaline phosphatase to induce osteoblast 
cell, and growth factors such as fibroblast growth factor-2 
(FGF-2) to increase fibroblast proliferation, and bone 
morphogenetic protein-2 (BMP-2) as a mature osteoblast 
marker were present. Osteoblast plays a direct role in 
bone formation, especially in bone matrix formation, 
involving non-collagenous protein and growth factors.9 
Acceleration in bone remodeling will increase orthodontic 
tooth movement.10

Bone resorption is a crucial process during which 
orthodontic tooth movement by resorbing alveolar bone 

occurs as orthodontic forces respond. In this process, 
osteoclast is the most important cell involved in cell 
mediation. Osteoclasts are found in physiologic periodontal 
ligaments as mature condition cells. Osteoclasts seems 
appear within days when orthodontic mechanical force 
is applied to produce tooth movement.3 Osteoclasts 
differentiate from stem cells pathways in haemopoietic 
lineage and the early precursors of osteoclasts are 
granulocyte-macrophage colony-forming units. Resorption 
process cascade involves several steps directed toward 
removing organic and anorganic structures of alveolar 
bone matrix by osteoclast so that orthodontic tooth 
movement occurs. After that, the unmineralized bone 
surface is replaced by apposition process with lining 
osteoblasts. Several enzymes such as MMPs, collagenases 
and gelatinases is produced by osteoblasts which have 
role in accessing mineralized bone. Local and systemic 
factors are important for osteoclast activation and induce 
the production of hydrogen ions, proteolytic enzymes in 
vacuole under the ruffled border.3 Tartrate-resistant acid 
phosphatase (TRAP-6) positive multinuclear cells are an 
enzyme which is localized within the ruffled border area 
as a osteoclast mature biomarker.11

Orthodontic tooth movement produces both a pressure 
area and a tension area. In the pressure area, periodontal 
ligament shows disorganization and diminution of ligament 
fiber production and vascular contriction. In the tension 
area, stimulation produced by the stretching of periodontal 
ligament fiber bundles results in an increase in fiber 
production.3,8 Osteoclasts appear in the pressure area and 
osteoblasts in the tension area. Osteoclasts in the tension 
area remain poorly understood.11

The utilization of marine biota for dental treatment has 
been developed. Stichopus hermanii is well recognized 
as a human food source. Stichopus hermanii contain 
active ingredients such as proteins 86% (80% collagens), 
glucosaminoglycans including hyaluronic acid, chondroitin 
sulphate, cell growth factor, eicosapentaenoic acid (EPA) 
and docosahexaenoic acid (DHA) that are important for 
tissue regeneration.12,13

Previous research showed that 3% Stichopus hermanii 
can decrease relapse biometric and increase FGF-2 
and collagen type 1 expression in relapse orthodontic 
compared with 2.5%. Stichopus hermanii can act as an 
anticandidal.10,14 Another research showed that Stichopus 
hermanii modulates the inflammatory responses, stimulates 
the activation and proliferation of fibroblasts and enhances 
the rapid production of collagen fiber networks with shorter 
healing times. The level of proinflammatory cytokines; 
IL-1α, IL-1β, and IL-6, are significantly reduced in 
Stichopus hermanii-treated wounds and stimulation tissue 
regeneration.15 The role of Stichopus hermanii in bone 
resorption in tension area orthodontic tooth movement has 
yet not been fully investigated. The aim of this study was to 
investigate the active ingredients of nanopowder Stichopus 
hermanii in bone resorption in tension area orthodontic 
tooth movement of Cavia cobaya.

Dental Journal (Majalah Kedokteran Gigi) p-ISSN: 1978-3728; e-ISSN: 2442-9740. Accredited No. 32a/E/KPT/2017.
Open access under CC-BY-SA license. Available at http://e-journal.unair.ac.id/index.php/MKG
DOI: 10.20473/j.djmkg.v50.i4.p188–193

http://dx.doi.org/10.20473/j.djmkg.v50.i4.p188-193


190 Prameswari and Brahmanta/Dent. J. (Majalah Kedokteran Gigi) 2017 December; 50(4): 188–193

MATERIALS AND METHODS

The study was conducted at experimental laboratories 
with completely randomized control group post-test only 
design. Ethical permission was obtained from the Ethics 
and Scientific Research Committee of Experimental Animal 
Use at the Faculty of Dentistry, Universitas Hang Tuah no 
125/KEPK/I/2016. Thirty-two male guinea pigs (Cavia 
cobaya) aged 2.5 months and weighing 200–300 grams, 
fed a standard pellet diet and tap water ad libitum, were 
randomly divided into four groups each consisting of eight 
guinea pigs. Based on previous research, the optimum 
Stichopus hermanii concentration used were 3%, while 
attempts to add concentrations of 3.5% Stichopus hermanii 
were made.10 A 10% ketamine injection was administered 
as an anesthetic, with 0.1–0.2 ml/kg for acepromazine 0.5 
ml, 10% buffered formalin and cotton.8 

In this research, Stichopus hermanii were taken from 
Raas Island Sumenep, East Java Indonesia and was cleaned 
by longitudinal incision using a scalpel without damaging 
the internal organs. The Stichopus hermanii were dried 
in ovens (U type, Memmert, Wisconsin, USA) at 28 
degrees centigrade, blended (model HGBTWT, Waring 
commercial, USA) and reduced to nanopowder (20 nm) 
by means of a High Energy Milling (Puspitek, Tangerang, 
Indonesia) method. Quantitative analysis of Stichopus 
hermanii active ingredients involved UV Vis Transmittance 
(T872) spectrophotometry (Intertek PTL, Pittsfield, USA) 
to examine flavonoid, gas chromatography (Agillent 
GC-MS 5975C, Palo Alto, CA, USA) to examine EPA 
and DHA and a reversed phase high performance liquid 
chromatography (HPLC J.T Baker, United States) with UV 
detection to examine chondroitin sulphate.10

To prepare nanopowder, 3% Stichopus hermanii gel 
was made from 0.3 gr Stichopus hermanii powder diluted 
with natrium carboxy methylcellulose (NaCMC) 2% in 10 
ml of dimethyl sulfoxide (DMSO) 5%. Nanopowder 3.5% 
Stichopus hermanii gel was made from 0.35 g Stichopus 
hermanii powder diluted with NaCMC 2% in 10 ml of 
DMSO 5%.10

The procedure within this study began with the 
acclimatization of 32 guinea pigs for 48 hours. The guinea 
pigs were divisibled became four groups of eight subjects: 
K(–) group as a negative control group (without treatment), 
K(+) group as a positive control group whose orthodontic 
tooth movement was triggered by means of an elastic 
separator at a force of 0.0474 kN, measured with a gauge 

name autograph (AGS-X Series, Shimadzu, Kyoto, Japan) 
during experiment and P1, P2 groups which were given 
with both orthodontic pressure and Stichopus hermanii 3% 
and 3.5% over 14 days. 0.025 ml of Stichopus hermanii gel 
was applied to the gingival sulcus tension area once per day 
with an insulin syringe.10

The research was conducted at the Biochemistry 
Laboratory Medical Faculty of Universitas Airlangga. The 
guinea pigs were monitored during the experiment all of, 
with all of the groups being sacrificed on the fourteenth 
day of the experiment. The maxillary incisive teeth 
were dissected and placed in 10% buffered formaline.10 
Histological sections were subsequently prepared with 
TRAP-6 immunohistochemistry as an osteoclast marker 
and then observed by using a light microscope (Nikon 
optiphot 2, Japan). 

The expression of TRAP-6 as osteoclast marker in 
the periodontal ligament on 1/3 apical in the tension area 
was observed. Photographs using an optilab advance 
(Miconos, Yogyakarta, Indonesia) were taken to measure 
the osteoclasts (TRAP-6) expression seen through a 
microscope at 400X enlargement. Each histological section 
was observed and calculated.10

Finally, the data was statistically measured using a 
statistical package for the social science (SPSS) version 
20. The resulting research data was tabulated, the statistical 
hypothesis being conducted with a standard analytic 
significance of 95% (p = 0.05) by one-way Anova test 
(analysis of variants) to analyze the difference of each 
variable compared with the control. The data was tested 
with LSD test (p < 0.05).

RESULTS

The data obtained from the quantitative analysis of 
Stichopus hermanii showed that the percentage of flavonoid 
was higher than the other active ingredients examined 
(Table 1). The data resulting from orthodontic tooth 
movement measurement showed that there were differences 
in orthodontic tooth movement width within each group. 
In the K(+) group, the mean was 0.45 mm, while the mean 
of the P1 group was 0.496 mm, and the mean of P2 group 
was 0.498 mm (Table 2 and Figure 1). 

Moreover, the data also showed that the TRAP-6 
expression as a osteoclast marker increased in P1 and P2 
groups. The highest number found in the P2 group treated 

Table 1. Active ingredients of nanopowder Stichopus hermanii

No. Active ingredients Result Method

1 Flavonoid (%) 5.3218 (%) Spectrophotometry (Saura-Calixto,1998; Larrauri et al, 1997)

2
Decosahexaenoic Acid (DHA) 
(mg/100g)

No Detection (< 1.20) Gas Chromatography

3 Eicosapentaenoic (EPA) (mg/100g) 17.10 mg/100 g Gas Chromatography

4 Condroitin sulphate (mg/100g) 706.15 mg/100 g 18-5-56/MU/SMM-SIG, HPLC

Dental Journal (Majalah Kedokteran Gigi) p-ISSN: 1978-3728; e-ISSN: 2442-9740. Accredited No. 32a/E/KPT/2017.
Open access under CC-BY-SA license. Available at http://e-journal.unair.ac.id/index.php/MKG
DOI: 10.20473/j.djmkg.v50.i4.p188–193

http://dx.doi.org/10.20473/j.djmkg.v50.i4.p188-193


191191Prameswari and Brahmanta/Dent. J. (Majalah Kedokteran Gigi) 2017 December; 50(4): 188–193

with nanopowder Stichopus hermanii 3.5% was 13.17 cell/
field of view. Meanwhile, in the negative control group, 
the mean was 9.67, and in K(+) group the mean was 8.5 
(Table 3 and Figure 3). TRAP-6 expression is showed in 
Figure 2. The statistical results with one-way Anova test 
confirmed that there were significant differences between 
all groups (p≤0.05). 

The statistical results of one-way Anova and LSD 
showed that there was a significant difference of TRAP-6 
expression as a osteoclast marker in the tension area 
between K(-), K(+) groups and the P1 and P2 groups. 
TRAP-6 expression was significantly increased in P2 
compare to K(+), P2 to K(-), P2 to P1, but P1 to K(+) had 
no significantly differences as seen in Table 4.

DISCUSSION

The results showed that the P2 group that was 
administered the orthodontic force separator rubber and 
Stichopus hermanii 3.5% had the widest orthodontic tooth 
movement (OTM) among the groups. Group P2 also had 
the highest TRAP-6 expression in the tension site compared 
to the K(–), K(+) groups.

Orthodontic tooth movement is a useful model for 
understanding the mechanism of bone remodeling induced 
by mechanical loading. Osteoclasts play an important role 
in OTM where osteoclast have a bone resorption function.11 
Osteoclastogenesis mechanisms at a physiologic level have 

Table 2. Descriptive mean and standard deviation of orthodontic 
tooth movement maxillary left central incisive (mm)

Group
Mean Standard Deviation

K(-) 0 0

K(+) 0.45 0.022

P1 0.496 0.008

P2 0.498 0.013

Table 3. Descriptive mean and standard deviation of TRAP-6 
expression in tension area (cell/field of view)

Group
TRAP-6 Expression

Mean Standard Deviation

K(-) 9.67 2.73

K(+) 8.5 1.22

P1 11.5 1.87

P2 13.17 2.13

Table 4. One-way Anova test of TRAP-6 expression in tension 
area

Variable
One-way 

Anova test
F Sig

TRAP-6
expression

Between group 5.933 0.005
Within group

Total

Table 5. LSD test of TRAP-6 expression in tension area

Variable
LSD Test

Sig

TRAP-6
expression

K(-) K(+) 0.763
P1 0.434
P2 0.038

K(+) P1 0.087
P2 0.004

P1 P2 0.514

Figure 2.  Imunohistological section of TRAP-6 expression in 
the control group (A), in the orthodontic group (B), 
in the orthodontic + Stichopus 3% group (C),), in the 
orthodontic + Stichopus 3.5% group (D) under a light 
microscope at 400× magnification.

Figure 1. Line chart mean of orthodontic tooth movement.

Figure 3. Mean and SD of TRAP-6 in tension area orthodontic 
tooth movement.

Dental Journal (Majalah Kedokteran Gigi) p-ISSN: 1978-3728; e-ISSN: 2442-9740. Accredited No. 32a/E/KPT/2017.
Open access under CC-BY-SA license. Available at http://e-journal.unair.ac.id/index.php/MKG
DOI: 10.20473/j.djmkg.v50.i4.p188–193

http://dx.doi.org/10.20473/j.djmkg.v50.i4.p188-193


192 Prameswari and Brahmanta/Dent. J. (Majalah Kedokteran Gigi) 2017 December; 50(4): 188–193

a function through the macrophage-colony stimulating 
factor (M-CSF) that induces osteoclast when there are no 
growth factor involved.3

In the tension area, TRAP-6 is found as positive 
multinuclear cells are localized within the ruffled border 
area as a osteoclast mature biomarker which has a relation 
with matrix remodeling.16 Osteoclasts which formed by 
chondrocytes or osteoblasts resorb the bone mineralized 
matrix. Osteoclasts are multinucleated giant cells dervied 
from hematopoietic cells. Osteoclast differentiation is 
dependent on two cytokines, a tumor necrosis factor (TNF) 
family cytokine, receptor activator of nuclear factor-
κB (NF-κB) ligand (RANKL) and M-CSF. M-CSF can 
stimulate monocyte proliferation. The cytokine receptor 
activator of nuclear factor-κB ligand (RANKL), which 
is secreted by mesenchymal stem cell and osteoblasts, 
stimulates monocyte differentiation into osteoclasts.16,17 
RANKL produced by osteoblasts or their precursors 
plays a role in osteoclast formation, thereby relation 
between bone formation to resorption.17 The interaction 
of RANKL with its receptor RANK results in a cascade of 
intracellular events including: NF-κB, mitogen-activated 
protein kinases (MAPKs), ionic calcium and calcium/
calmodulin-dependent kinase by recruiting the adaptor 
signal protein TNF receptor associated factor (TRAF6). 
As a result, a number of osteoclast-related marker genes, 
including: TRAP-6, calcitonin receptor (Ctr), cathepsin K 
(Ctsk) and nuclear factor of activated T cells (Nfatc1) are 
upregulated.16

Research with a mouse strain without RANKL, 
which can be conditionally deleted and made a series of 
Cre-deleter strains to showed that RANKL that controls 
mineralized bone resorption and bone remodeling 
produced by hypertrophic chondrocytes and osteocytes, 
where both embedded in bone matrix. Besides osteoblast, 
osteocyte RANKL have role for the bone loss associated 
with unloading.17 In the research reported here, the 
highest expression of TRAP-6 occurred in the P2 group 
that experienced the highest osteoclast activity resulting 
in matrix remodeling in the group given nanopowder 
Stichopus hermanii 3.5%. The P1 group administered 
with Stichopus hermanii 3% demonstrated no significant 
relationship with K(-) meaning that osteoclast for matrix 
remodeling in P1 group approached to normal physiologic 
condition. Osteoclastogenesis has a crucial role in bone 
homeostasis. Bone is preserved by active remodeling 
through the equilibrium between bone resorption by 
osteoclasts and bone apposition by osteoblasts.18

Previous research by Blummer into TRAP deficient 
mice confirmed that the formation of distinct bone relevant 
proteins and type I collagen were initiated at an earlier 
point in time. Osteopontin, another bone specific marker 
in TRAP deficient mice, directly modulates bone formation 
in a response to mechanical stress which is independent 
of its effect on osteoclasts. Runt related transcription 
factor 2 (Runx2) expression occurred at the same point 
in TRAP deficient mice and proved crucial for osteoblast 

differentiation.19,20 This indicated that TRAP-6 has a role 
in bone and matrix formation. Bone apposition can occur 
after TRAP-6 function in bone matrix remodeling.4

Nanopowder Stichopus hermanii contains various 
active ingredients such as flavonoid, EPA, DHA, triterpene, 
and glycosaminoglycans.13 EPA as a component of: 
nanopowder Stichopus hermanii is known to have a function 
in osteoclast differentiation. Osteoclast differentiation takes 
places through several steps, including: progenitor growth, 
differentiation to mononuclear pre-osteoclasts, cell fusion to 
multinuclear osteoclasts and the activation of osteoclasts to 
unique ability to resorb bone and EPA accelerated osteoclast 
fusion. In other ways, DHA can prevent osteoclastogenesis 
is also related to cell-cell fusion, as shown by mononuclear 
TRAP-positive osteoclasts.18,21

Osteoclastogenesis is also regulated by AP-1 as a 
transcription factor. AP-1 is a cell biosensor that can 
change extracellular signaling for cell function. When 
there is no AP-1 expressed in osteoblast, this can induce 
osteoclastogenesis through TRAP-6.22 Flavonoid is one 
active ingredient of Stichopus hermanii that can inhibit 
AP-1 and induce osteoclastogenesis.23–25

The application of nanopowder Stichopus hermanii in 
the tension area could induce M-CSF due to the effect of 
triterpene. Triterpene can induce caspase-3 and caspase-9.26 
Activated caspases play an important role in the degradation 
of specific nuclear proteins and induce osteoblastic 
differentiation.27 Accelerated bone formation in the 
tension area will induce bone resorption indirectly into 
the pressure area, thereby increasing biometric orthodontic 
tooth movement.28

Chondroitin sulphate is one glycosaminoglycan 
which have effect on another functionally with cytokines, 
kemokins, and growth factors in the alveolar bone 
element and structures where osteoblasts and osteoclasts 
cooperate to coordinate the process of bone remodeling. 
Glycosaminoglycan may help control osteoclastogenesis in 
microenvironments where osteoblasts/osteoclasts inherent. 
Glycosaminoglicans-bound RANKL block the interaction 
between RANKL and RANK.29 Glycosaminoglycan has 
affinity for RANKL and significantly prevents RANKL-
induced osteoclastogenesis by activating ERK pathway. 
Local interaction between bone cells is crucial factor 
for control bone remodeling and formation. The overall 
effect of glycosaminoglycan on osteoblasts is stimulatory, 
together with the ability of this glycosaminoglycan to 
prevent osteoclastogenesis. Glycosaminoglycan shifts 
the homeostasis of bone remodeling tends towards bone 
formation by preferencing osteoblastogenesis while 
antagonizing osteoclastogenesis.30 The stimulatory effect 
of bone formation in the tension area can induce bone 
resorption in the pressure area as a response to physiological 
mechanical stress.11

In conclusion, active ingredients of nanopowder 
Stichopus hermanii gel play a role in bone resorption in 
tension areas of orthodontic tooth movement. Nanopowder 
Stichopus hermanii 3.5% represented the optimum 

Dental Journal (Majalah Kedokteran Gigi) p-ISSN: 1978-3728; e-ISSN: 2442-9740. Accredited No. 32a/E/KPT/2017.
Open access under CC-BY-SA license. Available at http://e-journal.unair.ac.id/index.php/MKG
DOI: 10.20473/j.djmkg.v50.i4.p188–193

http://dx.doi.org/10.20473/j.djmkg.v50.i4.p188-193


193193Prameswari and Brahmanta/Dent. J. (Majalah Kedokteran Gigi) 2017 December; 50(4): 188–193

concentration containing the active ingredient flavonoid, 
EPA that can increase TRAP-6 expression as osteoclast 
activity to resorb periodontal ligament and alveolar bone 
in tension area orthodontic tooth movement.

REFERENCES

 1. Kementerian Kesehatan Republik Indonesia. Riset kesehatan dasar 
(RISKESDAS) 2013. Jakarta: Badan Penelitian dan Pengembangan 
Kesehatan Kementerian Kesehatan RI; 2013. p. 143–5. 

 2. de Almeida AB, Leite ICG, Melgaço CA, Marques LS. Dissatisfaction 
with dentofacial appearance and the normative need for orthodontic 
treatment: determinant factors. Dental Press J Orthod. 2014; 19(3): 
120–6. 

 3.  Krishnan V, Davidovitch Z. Cellular, molecular, and tissue-level 
reactions to orthodontic force. Am J Orthod Dentofac Orthop. 2006; 
129(4): 469.e1–32. 

 4.  Ariffin SHZ, Yamamoto Z, Abidin IZZ, Wahab RMA, Ariffin ZZ. 
Cellular and molecular changes in orthodontic tooth movement. Sci 
World J. 2011; 11: 1788–803. 

 5.  Proffit WR, Fields HW, Sarver DM. Contemporary orthodontics. 
4th ed. St Louis-Missouri: Mosby Elsevier; 2007. p. 75–84. 

 6.  Susilowati S. Peran matriks metaloproteinase-8 pada cairan 
krevikuler gingiva selama pergerakan gigi ortodontik. Dentofasial. 
2010; 9(1): 47–54. 

 7.  Alhadlaq AM. Biomarkers of orthodontic tooth movement in gingival 
crevicular fluid: a systematic review. J Contemp Dent Pract. 2015; 
16(7): 578–87. 

 8.  Prameswari N. The response of periodontal ligament collagen fibres 
and the thickness of inserting periodontal ligament fibre bundles 
at cementum pressure sites of fixed orthodontic appliances. Dent J 
(Maj Ked Gigi). 2007; 40(2): 70–5. 

 9.  Mohamed AM. An overview of bone cells and their regulating factors 
of differentiation. Malays J Med Sci. 2008; 15(1): 4–12. 

10.  Prameswari N, Soetjipto S, Rahayu RP. Osteogenesis at tension site 
by Stichopus hermanii application as relapse orthodontic prevention. 
Int J ChemTech Res. 2016; 9(6): 686–93. 

11.  Kitaura H, Kimura K, Ishida M, Sugisawa H, Kohara H, Yoshimatsu 
M, Takano-Yamamoto T. Effect of cytokines on osteoclast formation 
and bone resorption during mechanical force loading of the 
periodontal membrane. Sci World J. 2014; 2014: 1–7. 

12.  Bordbar S, Anwar F, Saari N. High-value components and bioactives 
from sea cucumbers for functional foods--a review. Mar Drugs. 2011; 
9: 1761–805. 

13.  Sendih S, Gunawan. Keajaiban teripang: penyembuh mujarab dari 
laut. Jakarta: Agro Media Pustaka; 2006. p. 13–49. 

14.  Revianti S, Soetjipto S, Rahayu RP, Parisihni K. Protective role of 
Sticophus hermanii ethanol extract supplementation to oxidative 
stress and oral hyperkeratosis in smoking exposed rats. Int J 
ChemTech Res. 2016; 9(5): 408–17. 

15.  Zohdi RM, Zakaria ZAB, Yusof N, Mustapha NM, Abdullah MNH. 
Sea cucumber (Stichopus hermanii) based hydrogel to treat burn 
wounds in rats. J Biomed Mater Res Part B Appl Biomater. 2011; 
98(1): 30–7. 

16.  Li J, Zeng L, Xie J, Yue Z, Deng H, Ma X, Zheng C, Wu X, Luo J, 
Liu M. Inhibition of osteoclastogenesis and bone resorption in vitro 
and in vivo by a prenylflavonoid xanthohumol from hops. Sci Rep. 
2015; 5: 1-14. 

17.  Xiong J, Onal M, Jilka RL, Weinstein RS, Manolagas SC, O’Brien 
CA. Matrix-embedded cells control osteoclast formation. Nat Med. 
2012; 17(10): 1235–41. 

18.  Akiyama M, Nakahama K, Morita I. Impact of docosahexaenoic 
acid on gene expression during osteoclastogenesis in vitro--a 
comprehensive analysis. Nutrients. 2013; 5: 3151–62. 

19.  Blumer MJF, Hausott B, Schwarzer C, Hayman AR, Stempel J, 
Fritsch H. Role of tartrate-resistant acid phosphatase (TRAP) in 
long bone development. Mech Dev. 2012; 129: 162–76. 

20.  Rodriguez-Carballo E, Gámez B, Ventura F. p38 MAPK signaling 
in osteoblast differentiation. Front cell Dev Biol. 2016; 4: 1–20. 

21.  Rahman MM, Bhattacharya A, Fernandes G. Docosahexaenoic acid 
is more potent inhibitor of osteoclast differentiation in RAW 264.7 
cells than eicosapentaenoic acid. J Cell Physiol. 2008; 214: 201–9. 

22.  Braun T, Zwerina J. Positive regulators of osteoclastogenesis and 
bone resorption in rheumatoid arthritis. Arthritis Res Ther. 2011; 
13: 1–11. 

23.  Shu S. Immunological effects of complementary and alternative 
medicine in allergy and astma. Disertation. California: University 
of California; 2008. p. 1–20. 

24.  Chi L, Gao W, Shu X, Lu X. A natural flavonoid glucoside, icariin, 
regulates Th17 and alleviates rheumatoid arthritis in a murine model. 
Mediators Inflamm. 2014; 2014: 1-10. 

25.  Osta B, Lavocat F, Eljaafari A, Miossec P. Effects of interleukin-17A 
on osteogenic differentiation of isolated human mesenchymal stem 
cells. Front Immunol. 2014; 5: 1–8. 

26.  Reyes-Zurita FJ, Pachón-Peña G, Lizárraga D, Rufino-Palomares 
EE, Cascante M, Lupiáñez JA. The natural triterpene maslinic 
acid induces apoptosis in HT29 colon cancer cells by a JNK-p53-
dependent mechanism. BMC Cancer. 2011; 11: 1–13. 

27.  Bell RAV, Megeney LA. Evolution of caspase-mediated cell death 
and differentiation: twins separated at birth. Cell Death Differ. 2017; 
24: 1359–68. 

28.  Nimeri G, Kau CH, Kheir NSA, Corona R. Acceleration of tooth 
movement during orthodontic treatment - a frontier in Orthodontics. 
Progress in Orthodontics. 2013; 14: 42.

29.  Savage JR, Pulsipher A, Rao NV., Kennedy TP, Prestwich GD, Ryan 
ME, Lee WY. A modified glycosaminoglycan, GM-0111, inhibits 
molecular signaling involved in periodontitis. PLoS One. 2016; 11(6): 
1–20. 

30.  L i ng L , Mu r a l i S, St e i n G S, va n Wijn e n A J, C o ol SM . 
Glycosaminoglycans modulate RANKL-induced osteoclastogenesis. 
J Cell Biochem. 2010; 109(6): 1222–31. 

Dental Journal (Majalah Kedokteran Gigi) p-ISSN: 1978-3728; e-ISSN: 2442-9740. Accredited No. 32a/E/KPT/2017.
Open access under CC-BY-SA license. Available at http://e-journal.unair.ac.id/index.php/MKG
DOI: 10.20473/j.djmkg.v50.i4.p188–193

http://dx.doi.org/10.20473/j.djmkg.v50.i4.p188-193